pharmacokinetics 3

Question 1

what is phase 1 of drug metabolism

Answer 1

active (pro-drug)
inactive
toxic
eg oxidation (cytochrome p450), reduction, hydrolysis (esterases)

Question 2

what is phase 2 of drug metabolism

Answer 2

drug solubilisation by conjugation
glucuronidation
acetylation
sulfation
methylation 
to elimination in urine or bile

Question 3

how are lipophilic drugs metabolised

Answer 3

phase 1 p450 to products of oxidation, reduction, hydrolysis to phase 2 conjugate to water-soluble metabolites

Question 4

what is a prodrug

Answer 4

a drug or compound that is metabolised into a pharmacologically active drug 
eg
enalapril to enalaprilat
codeine to morphine 
levodopa to dopamine

Question 5

what are cytochrome p450 inhibitors

Answer 5

Amiodarone
Ciprofloxacin
Erythromycin/Clarithromycin
Metronidazole
Fluconazole
Isoniazid
Alcohol (acute)
Grapefruit juice
rapid process to alter drug metabolism

Question 6

what are cytochrome p450 inducers

Answer 6

Carbamazepine
Phenytoin
Rifampicin
Alcohol (Chronic)
slow process

Question 7

what is the therapeutic index

Answer 7

Ratio of concentration associated with toxicity (MTC) vs concentration associated with efficacy (MEC)

Question 8

what happens to Cytochrome P450 metabolised drugs with

narrow therapeutic index

Answer 8

Drug metabolised
by CYP450 with
narrow therapeutic
index/window
Eg. warfarin, aminophylline + cytochrome p450 inhibitor
can have potential adverse drug interaction

Question 9

how do genetics link to drug metabolism

Answer 9

Genetic Polymorphisms are multiple genetic variants (allele combinations) which result in different phenotypes.
Polymorphisms of drug metabolising enzymes can affect drug handling.

Question 10

what is an extensive metaboliser

Answer 10

Two active ‘normal’ alleles

Question 11

what is an intermediate metaboliser

Answer 11

One normal and one abnormal allele

Question 12

what is a poor metaboliser

Answer 12

Two abnormal alleles

Question 13

what are ultrarapid metabolisers

Answer 13

Duplication of normal alleles

Question 14

what is CYP2D6 polymorphism with ultrarapid metaboliser effect

Answer 14

causes opiate toxicity in some individuals even at low dose

causes an exaggerated response to codeine

Question 15

what is CYP2D6 polymorphism with poor metaboliser effect

Answer 15

causes inadequate pain relief by codeine in some individuals

Question 16

how is activity of N-acetyltransferase genetically determined

Answer 16

Fast acetylators at increased risk of isoniazid hepatotoxicity
Slow acetylators at increased risk of isoniazid neuropathy
Slow acetylators at increased risk of drug-induced lupus with hydralazine